A major initiative for our section is to examine the role of exposure to putative relapse triggers (such as environmental cues and stress) through the use of ecological momentary assessment (EMA). We are conducting studies in heroin/cocaine-using methadone-maintained outpatients and in obese individuals who are in a weight-maintenance program. Participants carry electronic diaries to record the base rates of exposure to putative relapse triggers as well as the presence of these triggers during relapse. In the first completed study, we prospectively monitored the acute daily-life precipitants of craving for, and use of, cocaine and heroin. In a cohort design, 114 methadone-maintained cocaine- and heroin-abusing outpatients provided EMA data on handheld computers for up to 14,918 person-days (mean 130.9 days per participant, range 6-189). Of those 114, a total of 102 provided acute pre-craving or pre-use data and were thus included in the present analyses. Changes in reports of mood and exposure to putative drug-use triggers at random intervals during the five hours preceding each self-reported episode of drug craving or use, analyzed via repeated-measures logistic regression (SAS GLIMMIX macro). The five hours preceding drug use showed orderly increases in reports of Saw Drugs, Offered Drugs, Wanted to see what would happen if I used, Tempted to use out of the blue, Handled $10 or more, Angry, Worried, Criticized by others, Uncomfortable, and Good mood, but not Bored or Sad. The five hours preceding drug craving showed a different pattern of reports, e.g. an orderly increase in Sad but no increase in Good mood. These findings confirm that polydrug-abusing individuals can provide behavioral data in their daily environments using handheld computers, and that those data can reveal orderly patterns, including prospectively detectable harbingers of craving and use. We are also exploring the use of handheld electronic devices for treatment delivery in patients daily environment. In addition, we are using handheld electronic devices to improve outcome measurement in our randomized clinical trials. This aspect of our research derives from laboratory-animal data showing that stress-induced reinstatement of cocaine seeking and/or heroin seeking can be prevented with the alpha-adrenergic agonist clonidine, while cue-induced reinstatement of such drug seeking can be prevented with aripiprazole. We are conducting two trials of clonidine, one to evaluate its effect on response to stress and drug cues, and the second to evaluate its efficacy in relapse prevention. We are currently conducting a study in which methadone-maintained outpatients carry handheld computers throughout the day to provide real-time data on cravings for heroin and cocaine, lapses to drug use, and base rates of putative lapse precipitants. We have demonstrated the feasibility of this form of data collection in our population and are using it in the clonidine trial to determine whether clonidines relapse-prevention effect is specific to subtypes of relapse. Finally, we completed a collaboration with investigators at the University of Chicago on a two-site study to investigate the time course of craving in abstinent smokers, with particular attention to the possibility of incubation, a phenomenon seen in preclinical studies, in which craving increases with duration of abstinence. Data analysis is underway, and a manuscript is in preparation. Incubation of craving may help explain the long-lasting vulnerability to relapse in individuals formerly dependent on nicotine, alcohol, or illicit drugs.